The primary objective of this work is to elucidate the cellular and synaptic mechanisms responsible for the genesis of spontaneous rhythmic activity in the developing spinal cord. Experiments are performed on isolated preparations of the chick and mouse spinal cords maintained in vitro. We use electrophysiological, optical and anatomical methods to analyze the function and properties of the developing networks. Recently we formulated a quantitative and qualitative model to account for the genesis of rhythmic activity by developing spinal networks. Crucial to this model are our recent observations that network activity and synaptic transmission are depressed after a spontaneous episode. This depression arises in part because of a decrease in the responsiveness of postsynaptic glutamate and GABA receptors. We have also been investigating the spontaneous activity generated by the lumbosacral cord of the fetal mouse. We have found that activity comprises large recurrent depolarizations that can be recorded from the ventral roots. In neonatal cords (P3) it has been possible to activate another network that may be the precursor of the adult locomotor network. Once active, this network drives contralateral motoneurons to discharge in an alternating manner. Imaging studies are currently in progress to identify the interneurons responsible for this pattern of activity.